Yan Miao, Wu Zhu-Feng, Tang Dan, Wang Feng, Xiao Yi-Wen, Xu Ping, Zhang Bi-Kui, Liu Yi-Ping, Xiang Da-Xiong, Banh Hoan Linh
Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China; Institute of Clinical Pharmacy, Central South University, Changsha, Hunan 410011, China.
Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China; Institute of Clinical Pharmacy, Central South University, Changsha, Hunan 410011, China; School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu 211100, China.
Biomed Pharmacother. 2018 Dec;108:60-64. doi: 10.1016/j.biopha.2018.08.121. Epub 2018 Sep 11.
Voriconazole (VRC) and proton pump inhibitors (PPIs) have similar metabolic pathways. The objectives of the study are to evaluate the impact of PPIs on the pharmacokinetics of VRC. Human liver microsomes model was applied to assess the inhibitory effects of PPIs on the metabolism of VRC in vitro. A retrospective study was also carried out to explore the relationship between the plasma VRC trough concentrations and PPIs uses. Patients were divided into six groups: control (n = 166), lansoprazole (LAN, n = 38), esomeprazole (ESO, n = 19), omeprazole (OME, n = 45), pantoprazole (PAN, n = 43), and ilaprazole (ILA, n = 38) groups. All five PPIs showed concentration-dependent inhibitory effects on the VRC metabolism in human liver microsomes, among which LAN, OME and ESO were three of the most potent inhibitors. Consistently, co-administered with LAN, OME and ESO significantly increased the plasma VRC trough levels (p < 0.05), whereas there was no significant association between VRC concentrations and PAN or ILA use. Interestingly, patients in the PPIs groups were more likely to reach the therapeutic VRC range of 1-5.5 μg/mL in steady state when compared with control patients (75-81% VS 69%). In conclusion, although all PPIs showed inhibitory effects on the VRC metabolism in vitro, only LAN, OME and ESO significantly increased VRC plasma concentrations. This study should be helpful for choice of the type of PPIs for patients administered with VRC.
伏立康唑（VRC）与质子泵抑制剂（PPI）具有相似的代谢途径。本研究的目的是评估PPI对VRC药代动力学的影响。应用人肝微粒体模型在体外评估PPI对VRC代谢的抑制作用。还进行了一项回顾性研究，以探讨血浆VRC谷浓度与PPI使用之间的关系。患者分为六组：对照组（n = 166）、兰索拉唑（LAN，n = 38）、埃索美拉唑（ESO，n = 19）、奥美拉唑（OME，n = 45）、泮托拉唑（PAN，n = 43）和艾普拉唑（ILA，n = 38）组。所有五种PPI对人肝微粒体中VRC的代谢均表现出浓度依赖性抑制作用，其中LAN、OME和ESO是最强的三种抑制剂。一致地，与LAN、OME和ESO联合使用显著提高了血浆VRC谷水平（p < 0.05），而VRC浓度与PAN或ILA的使用之间无显著关联。有趣的是，与对照组患者相比，PPI组患者在稳态时更有可能达到1 - 5.5μg/mL的VRC治疗范围（75 - 81%对69%）。总之，尽管所有PPI在体外均对VRC代谢表现出抑制作用，但只有LAN、OME和ESO显著提高了VRC血浆浓度。本研究应有助于为接受VRC治疗的患者选择PPI类型。
